Usage Guidelines and Precautions for Norethisterone
Norethisterone is a versatile synthetic progestin that can be used for hormone replacement therapy, contraception, and management of abnormal uterine bleeding, with dosing and precautions varying based on the specific indication.
Indications and Dosing
Hormone Replacement Therapy
- For women with intact uterus receiving estrogen therapy:
- Natural micronized progesterone is preferred over norethisterone for HRT due to its more favorable cardiovascular and thrombotic risk profile 1, 2
Contraception
- Progestin-only pill: Daily administration at the same time (within 3-hour window) 3
- Perfect use failure rate: 0.3%; typical use failure rate: 9% (due to missed pills) 3
- Requires backup contraception (condom + spermicide) for 48 hours if taken >3 hours late 3
Abnormal Uterine Bleeding
- Acute management: 10-30 mg daily, with higher doses for severe bleeding 4
- Effective at stopping bleeding within an average of 46 hours 4
- Therapeutic doses (10-20 mg) correspond to 20-30 μg ethinylestradiol due to partial conversion 5
Mechanism and Special Considerations
Unique Properties
- Norethisterone partially converts to ethinylestradiol in the body 5
- Has pronounced effects on the endometrium, making it effective for treating abnormal uterine bleeding 5
- Demonstrates beneficial effects on bone mineral density 5
Safety Profile
Cardiovascular Considerations
- At contraceptive doses: Similar thrombotic risk profile to levonorgestrel-containing contraceptives 6
- At higher therapeutic doses: Potentially increased risk of venous thromboembolism due to conversion to ethinylestradiol 5
- For patients with high thrombotic risk, medroxyprogesterone acetate may be preferable 1
Cancer Risk
- Long-term use associated with slightly increased breast cancer risk 5
- Should not be used longer than 6 months continuously to prevent meningioma occurrence 1
Contraindications and Precautions
Absolute Contraindications
- Current or history of venous thromboembolism 1
- Current or history of arterial thrombotic disease 1
- Known or suspected breast cancer 3
- Severe liver disease 3
- Unexplained vaginal bleeding 3
Relative Contraindications (Category 3 - Risks Usually Outweigh Benefits)
- Complicated solid organ transplantation (graft failure, rejection) 1
- Multiple risk factors for cardiovascular disease 1
- Migraine with aura (due to partial conversion to ethinylestradiol) 5
Drug Interactions
- HIV/HCV protease inhibitors and non-nucleoside reverse transcriptase inhibitors may significantly alter progestin concentrations 3
- Ulipristal acetate: Wait 5 days after ulipristal before starting norethisterone 3
- May affect laboratory tests: decreased SHBG concentrations and thyroxine levels 3
Special Populations
Adolescents
- Safe and effective for postpubertal adolescents 3
- Not indicated before menarche 3
- Effective for managing abnormal uterine bleeding in adolescents 4
Breastfeeding Women
- Small amounts pass into breast milk 3
- Generally no adverse effects on breastfeeding performance or infant development 3
- Isolated cases of decreased milk production reported 3
Practical Guidance
Patient Counseling Points
- Must be taken at the same time every day for contraceptive effectiveness 3
- Common side effects include menstrual irregularities 3
- Report prolonged bleeding, amenorrhea, or severe abdominal pain 3
- Barrier methods recommended if at risk for STIs/HIV 3
Monitoring
- Regular follow-up to assess symptom control, side effects, and compliance 2
- Initial follow-up at 3-6 months, then annually 2
Cycle Control
- Poorer cycle control compared to levonorgestrel-containing pills 7
- Consider 1 mg or synphasic preparation if cycle control is an issue 7
By understanding these guidelines and precautions, healthcare providers can appropriately prescribe norethisterone while minimizing risks and maximizing benefits for patients.